The overall goal of this program is the translational development of radioisotope carrier molecules and strategies to deliver systemic radiotherapy to cancer. This core is central to the development and the translation of these molecules and supports all of the projects: (1) preparing newly constructed molecules as radioconjugates for developmental studies, in vitro analysis, in vivo mouse studies and testing preliminary pharmaceutical lots and preparing IND documents for future clinical studies; (2) translating chemistry from the projects to standard methods to conjugate and radiolabel selected constructs as radiopharmaceuticals with optimized yields, stability, and reproducible quality; (3) assuring stability and quality of reagents for pharmaceutical development based on rigorous evaluation of vitro quality controls, kinetics and tolerance in mice; and (4) maintaining records in accordance with RUC, IRB, FDA and radiation use regulatory agencies. During the current funded period, this core developed simplified procedures to radiolabel MAbs with Y-90 with high yields and radiopharmaceutical quality using macrocyclic peptide linker chelating agents developed in the third project. Enhanced hepatic clearance of radioactivity seen in mice was substantiated by the excellent tumor targeting and decrease radiation dose to liver with Lym-1 and m170 DOTA-peptide pharmaceuticals prepared by this core for clinical studies in the first and second projects. The proposal for this core for the new grant period includes transfer of chemistry of molecular agents produced by each project to allow additional pharmaceutical development, chelate conjugation, PEG lot syntheses, SHALs q.c., optimization of radiometal labeling, and studies to assure stability in vitro and in vivo. This includes preparing radiopharmaceuticals for all three projects preclinical studies, using simplified, high yield procedures already developed to minimize expense and radiation exposure. DOTA chelate linkers for "on demand" cleavage from the combinatorial libraries in the third project, DOTA-SHALs from the first project, and DOTA-(scFv)4 PEG from the second project are undergoing in vitro evaluation and studies in non tumored mice to assess stability and tolerance. This core will continue to develop the methods for pharmaceutical grade production, purification, conjugation, quality control, storage and radiolabeling and final mouse and patient lot (and dose) release criteria for these novel radiopharmaceuticals.